中国中药杂志

2019, v.44(19) 4257-4262

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UPLC-MS/MS测定丹参川芎对药中4种酚酸类成分在大鼠血浆和心脏组织的药代动力学
Pharmacokinetics of four phenolic acids from Danshen-Chuanxiong drug pair in plasma and heart tissue of rats by UPLC-MS/MS

张翠英;章洪;任伟光;董宇;
ZHANG Cui-ying;ZHANG Hong;REN Wei-guang;DONG Yu;Guang'anmen Hospital,China Academy of Chinese Medical Sciences;Henan University of Traditional Chinese Medicine;

摘要(Abstract):

建立了UPLC-MS/MS测定4种酚酸类成分(丹酚酸B、紫草酸、迷迭香酸和阿魏酸)在大鼠血浆和心脏组织中药物浓度的分析方法,并应用其血药浓度(或组织分布浓度)和主要药动学参数阐释丹参川芎对药配伍的体内作用机制。丹参多酚酸及川芎纯化物单用或联用,注射给药后收集不同时间点的腹主动脉血和心脏组织,以Acquity UPLCBEH C18(2. 1 mm×50mm,1. 7μm)为色谱柱分离,以乙腈-0. 15%甲酸水溶液为流动相梯度洗脱,采用电喷雾离子源负离子模式扫描,多反应监测模式(MRM)检测血浆和心脏组织中上述4种酚酸类成分。结果显示,4种酚酸类成分在相应范围内具有良好线性关系,其精密度、准确度、稳定性及基质效应结果均符合生物样品定量分析要求。丹参多酚酸和川芎纯化物联用后,血浆中丹酚酸B和阿魏酸的AUC分别增加了40%和100%以上,而相应的Vd,CL显著降低;血浆中迷迭香酸的t1/2和Vd也显著增加了144. 6%,138. 7%;血浆中紫草酸的各项药动学参数无显著差异; 4种酚酸类成分集中分布到心脏组织的浓度明显高于单独给药组,该结果充分阐释了丹参川芎对药配伍的体内协同作用机制。
This study is to investigate the compatibility mechanism of Danshen-Chuanxiong drug pair on the pharmacokinetics of four phenolic acids. A UPLC-MS/MS method for quantitative determination of salvianolic acid B( Sal B),rosmarinic acid( RA),lithospermic acid( LA) and ferulic acid( FA) in plasma and heart tissue of rats was established. After single salvianolic acids and Chuanxiong-extract or combined intravenous infusion was given to rats,plasma samples and heart tissues in different time were collected. The chromatographic separation was performed on a BEH C18 column using 0. 15% formic acid-acetonitrile as mobile phase for gradient elution. A triple-quadrupole tandem mass spectrometry equipped with an electrospray ionization source was used as detector operating on multiple-reaction monitoring( MRM) scanning in negative ionization mode. Full validation of UPLC method including calibration curves,accuracy,precision,repeatability and matrix effect was investigated to comply with quantitative analysis requirements for biological samples. There were significant differences in the major pharmacokinetic parameters of Sal B,FA and RA for intravenous infusion of salvianolic acids and Chuanxiong-extract or combined in rat plasma. The AUC of Sal B and FA were increased above 40% and100%,respectively. Their Vd and CL were dropped evidently. t1/2 and Vd of RA increased above 130%. The concentration of four phenolic acids were all increased obviously in heart tissue comparing with single infusion. These results demonstrated that the compatibility mechanism of Danshen-Chuanxiong drug pair showed synergistic effect.

关键词(KeyWords): 酚酸类成分;UPLC-MS/MS;药代动力学;血浆;心脏
phenolic acids;UPLC-MS/MS;pharmacokinetics;plasma;heart tissue

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81202932)

作者(Author): 张翠英;章洪;任伟光;董宇;
ZHANG Cui-ying;ZHANG Hong;REN Wei-guang;DONG Yu;Guang'anmen Hospital,China Academy of Chinese Medical Sciences;Henan University of Traditional Chinese Medicine;

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DOI: 10.19540/j.cnki.cjcmm.20190619.203

参考文献(References):

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